Catalytic
nucleic acids and ligand-binding RNA and DNA aptamers have been
discovered in nature and also have been derived by using in
vitro evolution. As sequencing methods have become common, one
theme that has emerged in biology is that proteins have recognizable
domains that can be repeated, divided, or recombined in many ways.
As the number of examples of nucleic acid domains grows, it has
been shown that nucleic acid domains as well can be recombined in
the laboratory. Interestingly, recently discovered riboswitches
provide natural examples of multi-domain RNAs that exhibit this
modular character.
Multi-functional nucleic acids can be engineered
in the laboratory by linking together two or more separate domains
in a fashion that makes them become interdependent. The junction
structures can be derived either by using in vitro evolution or
by modular rational design which uses rules of secondary structure
to predict junction structures. In some cases, the junctions are
themselves modular and can serve as general relays of conformational
status between any two functional domains. These junctions are known
as communication modules.
The structural plasticity of nucleic
acids makes them excellent substrates for directed engineering efforts.
In addition, structured nucleic acids in living cells can present
a focus for therapeutic applications. The development of nucleic
acids as practical devices and as natural drug targets is a significant
focus of the Breaker laboratory.